Intact-Cell MALDI-ToF Mass Spectrometry for the Authentication of Drug-Adapted Cancer Cell Lines

Area of Science:

• Biotechnology
• Cell Biology
• Analytical Chemistry

Background:

• Cell line misidentification poses a significant challenge in scientific research.
• Short tandem repeat (STR) analysis is the standard for cell line genetic origin identification but cannot differentiate sublines.
• A need exists for methods to authenticate cell lines with shared genetic origins.

Purpose of the Study:

• To evaluate intact cell MALDI-ToF mass spectrometry for differentiating neuroblastoma cell lines and their drug-adapted sublines.
• To assess the potential of MALDI-ToF mass spectrometry as an authentication method for mammalian cell lines of common genetic origin.

Main Methods:

• Intact cell MALDI-ToF mass spectrometry was applied to three parental neuroblastoma cell lines (IMR-5, IMR-32, UKF-NB-3) and eleven drug-adapted sublines.
• Principal component analysis (PCA) was used to analyze the mass spectrometry data and identify differences between cell lines.
• Whole-cell mass spectrometry fingerprints were generated for each cell line.

Main Results:

• PCA of MALDI-ToF mass spectrometry data revealed distinct patterns differentiating most, but not all, cell lines.
• The method successfully separated the parental cell line IMR-32 from its clonal subline IMR-5.
• Drug-adapted sublines, including cisplatin/oxaliplatin-resistant and vincristine/vinblastine-adapted lines, exhibited unique mass spectrometry patterns.

Conclusions:

• Intact whole-cell MALDI-ToF mass spectrometry demonstrates potential for distinguishing between cell lines with a common genetic background.
• This technique could be developed into a valuable tool for cell line authentication, complementing existing methods.
• The findings suggest MALDI-ToF mass spectrometry can identify subtle molecular differences arising from drug adaptation or clonal variation.